{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:49:41Z","timestamp":1791575381344,"version":"4.3.4"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Boehringer Ingelheim"},{"name":"Eli Lilly and Company"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"abstract":"\n Key Points<\/jats:title>\n \n \n \n The kidney failure risk equation showed excellent discrimination for treated kidney failure outcome in patients with CKD.<\/jats:p>\n <\/jats:list-item>\n \n In a wide range of causes of CKD, urine tubular biomarkers improved prediction of kidney disease progression beyond established clinical risk models.<\/jats:p>\n <\/jats:list-item>\n \n EGF, kidney injury molecule-1, and monocyte chemoattractant protein-1 added the most prognostic value.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Urine tubular biomarkers have previously been associated with chronic kidney disease (CKD) progression independently of eGFR and albuminuria. We evaluated whether nine urine tubular biomarkers could improve prediction of kidney failure beyond serum creatinine and urine albumin\u2011creatinine ratio among adults with CKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Among 5100 participants in Study of Heart and Kidney Protection With Empagliflozin, a randomized trial that assessed the effects of empagliflozin 10 mg versus matching placebo among patients with CKD at risk of progression, nine urine creatinine-indexed tubular biomarkers were measured, including\n \u03b1<\/jats:italic>\n \u20101 microglobulin, dickkopf-3, EGF, interleukin-18, kidney injury molecule\u20101 (KIM\u20101), monocyte chemoattractant protein\u20101 (MCP\u20101), neutrophil gelatinase-associated lipocalin, uromodulin, and human cartilage glycoprotein-40. Outcomes were kidney disease progression (treated kidney failure, renal death, or sustained \u226540% eGFR decline) and treated kidney failure (maintenance dialysis or kidney transplant). Relative to models based on the linear predictor of the kidney failure risk equation (KFRE), improvements in discrimination were estimated with further addition of the nine tubular biomarkers using absolute difference in Uno C-index.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Over a median 3.5 years of follow-up, 1191 participants experienced kidney disease progression and 461 experienced treated kidney failure. KFRE demonstrated excellent discrimination for treated kidney failure (C-index 0.858 [0.840\u20130.874]) and moderate discrimination for kidney disease progression (0.724 [0.705\u20130.743]). Addition of three biomarkers (MCP-1, KIM-1, and EGF) most strongly associated with CKD outcomes yielded some further improvement in predicting kidney failure (absolute difference 0.014 [0.009\u20130.024]) and kidney disease progression (0.038 [0.026\u20130.053]). Prediction of kidney outcomes was only slightly improved when further expanding from three to all nine tubular biomarkers.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In a wide range of causes of CKD, adding three urine tubular biomarkers (MCP-1, KIM-1, and EGF) to KFRE improves estimates of risk of CKD progression.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n NCT03594110.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000001203","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:25Z","timestamp":1788454825000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Predictive Value of Urine Tubular Biomarkers on Kidney Outcomes"],"prefix":"10.2215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7940-386X","authenticated-orcid":false,"given":"Greco B.","family":"Malijan","sequence":"first","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-8243","authenticated-orcid":false,"given":"William G.","family":"Herrington","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0083-3649","authenticated-orcid":false,"given":"Parminder K.","family":"Judge","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Sardell","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6688-1576","authenticated-orcid":false,"given":"Daniel","family":"Chapman","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Wolfson Laboratory, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-6105","authenticated-orcid":false,"given":"Michael","family":"Hill","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Wolfson Laboratory, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0917-4968","authenticated-orcid":false,"given":"Stewart","family":"Moffat","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Wolfson Laboratory, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8470-8430","authenticated-orcid":false,"given":"Doreen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-9476","authenticated-orcid":false,"given":"Alfred K.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Steubl","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany"},{"name":"Department of Nephrology, Hospital Rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-827X","authenticated-orcid":false,"given":"Martin J.","family":"Landray","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-5301","authenticated-orcid":false,"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Baigent","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-0023","authenticated-orcid":false,"given":"Richard","family":"Haynes","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9869","authenticated-orcid":false,"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-4418","authenticated-orcid":false,"given":"Natalie","family":"Staplin","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health, Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-204X","authenticated-orcid":false,"given":"Michael G.","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, 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